Comparing additive effect of dexmedetomidine and neostigmine to bupivacaine on postspinal anesthesia cesarean section induced pain intensity: A health promotion Approach

Abstract

BACKGROUND:

This study pursued the goal to evaluate the effect of dexmedetomidine and neostigmine on pain, sedation, and locomotor properties during and after surgery in the patients receiving intrathecal bupivacaine for spinal anesthesia in women with elective cesarean section (CS) and to assess the effective dose of dexmedetomidine and neostigmine.

MATERIALS AND METHODS:

The present clinical trial study was performed on the women as the candidates for elective CS between 2022 and 2023 in Imam Khomeini Educational and Medical Center located in Mazandaran province. The patients for spinal anesthesia were divided into two groups: (1) receiving bupivacaine and dexmedetomidine (1 μg) and (2) receiving bupivacaine and neostigmine (10 μg). Bromage, Visual Analog Scale, and Ramsay scores were recorded in each patient at the intervention time, 2, 4, 8, and 12 h after the onset of anesthesia, along with the demographic and clinical baseline characteristics. The generalized statistical estimating model (GEE) was used to compare the variance of the aforementioned criteria between the two groups. The statistical significance level of 0.05 was used, and all statistical analyses were conducted using STATA/MP. 17: Stata|; M Statistical Software: Release 17. College Station, TX: StataCorp LLC.

RESULTS:

One hundred ten individuals participated in this study. The study participants’ mean age was 31.56 ± 5.92. The level of pain intensity in group 1 was lower than that of group 2, which was statistically significant (P < .001). In the GEE and after controlling the effects of the variables including age, body mass index and mean arterial blood pressure, it was found that the mean score of pain intensity score in group 2 was 0.75 (the confidence limits 0.59 equal to 0.59–0.91), which was more than that of group 1 (P < .001).

CONCLUSION:

Using dexmedetomidine exerts a greater and better effect on reducing pain intensity and boosts the sedative effect of neostigmine in the patients undergoing CS. It is suggested to run a study with a larger statistical community to deal with this issue. The results of this study can be useful in making prevention decisions and maintaining performance of women.

Introduction

Local analgesic techniques decrease the neuroendocrine stress response, thromboembolic phenomenon and the requirement for the postoperative period injectable analgesics.[1,2,3] The duration of effective analgesia depends on the dose and concentration of local anesthetics. As the volume and concentration increases, the local anesthetic systemic toxicity will get higher. Opioids prolong postoperative analgesia and enhances the quality of analgesia; on the other hand, they lead to urinary retention, sedation, and itching.[4] Non-narcotics like clonidine, ketamine, neostigmine, tramadol, midazolam, and dexmedetomidine were evaluated as epidural adjuvants.[3,5,6] Spinal anesthesia is typically used in CS surgeries. Apart from being economical and easy to use, spinal anesthesia provides rapid anesthesia and muscle relaxation.[7,8] Yet, using local anesthetics alone is of ephemeral effect and not sufficient to avert visceral pain and nausea, particularly in the early stages.[9,10,11,12] Visceral pain is common during spinal anesthesia with low-dose local anesthetics. This issue will be particularly burdensome in cesarean surgery because surgeons have to lift the uterus and suture the peritoneum during surgery.[13] Administering adjuvant analgesics is a well-accepted method in clinical applications to overcome the shortcoming of local anesthesia. The evidence from animal studies indicates that similar to clonidine, dexmedetomidine results in spinal anesthesia.[14] It has been revealed that intrathecal α-2 adrenergic receptor agonists can manage somatic and visceral pain.[15] Intrathecal dexmedetomidine of doses 3, 5, 10, and 15 μg with bupivacaine has been used in surgeries like lower extremity and transurethral prostatectomy.[15,16,17,18,19,20] Intrathecal dexmedetomidine has also been used in CS. As shown by Sun et al., adding 10 μg dexmedetomidine to bupivacaine provides better intraoperative and postoperative analgesia,[21] Li et al. reported the same data that dexmedetomidine at dose 10 μg plus bupivacaine was sufficient for intraoperative anesthesia and postoperative analgesia.[22] The intrathecal injection of muscarinic receptor agonists produces an analgesic effect in rats,[23] which is reversed (neutralized) by intrathecal atropine.[24] Intrathecal neostigmine induces analgesia to experimental pain stimuli in normal volunteers,[25] and also the patients with chronic pain[26] and after surgery.[27,28] These studies suggest that stimulating the spinal cholinergic receptor causes analgesia in humans as well as animals, which is probably associated with interaction with muscarinic receptors.

Intrathecal neostigmine also produces dose-dependent and severe nausea, which is practically prohibited for clinical use. Recently, epidural neostigmine administration has been proposed for patients suffering from chronic pain[29,30] and after surgery without creating nausea.[31,32,33,34,35] Regional anesthesia, particularly spinal anesthesia, is a cornerstone of modern cesarean section (CS) surgery, offering numerous advantages. However, the inherent limitations of local anesthetics, such as short duration of action and potential for inadequate visceral analgesia, necessitate the exploration of adjuvants to optimize anesthetic efficacy and patient outcomes.[36] Traditional adjuvants like opioids, while effective in prolonging analgesia, can have undesirable side effects such as nausea, vomiting, and respiratory depression. Alpha-2 adrenergic agonists, such as clonidine and dexmedetomidine, have emerged as promising alternatives, demonstrating both analgesic and anesthetic properties with improved hemodynamic stability.[37] Intrathecal administration of dexmedetomidine has shown promise in various surgeries, including CS, by providing enhanced intraoperative and postoperative analgesia when combined with bupivacaine.[38]

The importance of local analgesic techniques in surgical procedures, particularly CSs, cannot be overstated.[39] These techniques play a crucial role in minimizing the neuroendocrine stress response and reducing the risk of thromboembolic phenomena, thereby enhancing patient safety and recovery. By effectively managing postoperative pain, local anesthetics decrease the reliance on injectable analgesics, particularly opioids, which can lead to undesirable side effects such as sedation and urinary retention.[40] The incorporation of adjuvant medications, such as clonidine and dexmedetomidine, further optimizes pain management by prolonging analgesia and improving the quality of pain relief. This multifaceted approach not only addresses the limitations of traditional local anesthetics but also aligns with enhanced recovery after surgery protocols, ultimately leading to better patient outcomes and satisfaction.[41] As such, ongoing research into these techniques is vital for advancing anesthetic practices and improving the overall surgical experience for patients. Because of dexmedetomidine and neostigmine side effects, these drugs usually less applied by anesthesiologists as neuraxial adjuvants. The present research assigned to investigate the effect of low dose dexmedetomidine and neostigmine as adjuvant medications in the patients undergoing CS.

Material and Methods

Study design and setting

The present study was a randomized, double-blind controlled clinical trial on patients referred to Imam Khomeini Hospital in Sari (Iran) to determine the effect of low-dose dexmedetomidine and neostigmine as adjuvant medications in the patients undergoing CS.

Study participants and sampling

This study was conducted on 110 patients of Imam Khomeini Hospital in Sari (Iran), using N = ([Z1-α/2 + zβ] 2s2)/(µ1-µ2) 2 formula.

Data collection tool and technique

The patients who met the inclusion criteria were divided into two intervention groups, A and B, using the block randomization method.

Preoperative procedures

Patient Preparation: Patients were admitted to the operating room, and routine monitoring was initiated (blood pressure, pulse oximetry, etc.).

Anesthesia Induction: Spinal anesthesia was administered using a 27G needle at the L3–L4 or L4–L5 intervertebral space.

Intervention

• Drug administration: Control Group: Patients received 12 mg of hyperbaric bupivacaine

• Experimental Group 1: Patients received 12 mg of hyperbaric bupivacaine and 1 µg of intrathecal dexmedetomidine

• Experimental Group 2: Patients received 12 mg of hyperbaric bupivacaine and 10 µg of intrathecal neostigmine.

Following the patient’s admission to the operating room, an 18 G catheter was used to get a peripheral vein, and a prescription for Ringer’s lactate solution (250 cc) and 1 g of cefazolin was written as a preventative measure. The patient was put to sleep in a seated position for anesthesia after their blood pressure, pulse oximetry, and other vital signs were checked. Under local anesthetic with 2% lidocaine and no vasoconstrictor, a 27 g needle was used to puncture the spine through the L3–L4 or L4–L5 intervertebral spaces. The patients received 2.5 cc hyperbaric bupivacaine 0.5% (12 mg) for intrathecal anesthesia. Patients in group 1 were given 1 μg intrathecal dexmedetomidine together with bupivacaine, while patients in group 2 were given 10 μg intrathecal neostigmine along with bupivacaine. Depending on the patient group, one of the anesthesia assistants administered bupivacaine plus either neostigmine or dexmedetomidine to the anesthesiologist. In this sense, the anesthesiologist was ignorant of neostigmine or dexmedetomidine. Following anesthesia, the patients were turned onto their backs, with the uterus being manually moved to the left side in order to relieve strain on the inferior vena cava. The patients received 2–3 L of nasal oxygen per minute. To treat hypotension, phenylephrine and Ringer’s lactate were administered. Maintaining the patient’s blood pressure over 100 mmHg was the goal. Atropine (0.5 mg) was utilized in cases of bradycardia (heart rate less than 45). To induce uterine contractions after birth, oxytocin was given as a diluted solution in Ringer’s lactate.

Postoperative monitoring

Vital signs (blood pressure, heart rate, oxygen saturation) were monitored continuously.

Pain intensity was assessed using the Visual Analog Scale (VAS).[42]

Motor block was assessed using the Bromage Scale.

Sedation level was assessed using the Ramsay Sedation Scale.

Adverse effects like nausea, vomiting, and hypotension were monitored.

Following surgery, the patient was provided antiemetic medication and painkillers in the usual manner. The medication ondansetron (4 mg) was prescribed for nausea and vomiting. When spinal anesthesia was applied, the following parameters were recorded: the length of time the patient was unconscious and analgesic, the fluctuation of the mean arterial blood pressure (MAP), the percentage of oxygen saturation, heart rate, the newborn’s Apgar score, the Bromage score for motor block, the VAS score for pain, and the Ramsay scale score for sedation at zero, 2, 4, 8, and 12 h later.

Visual Analog Scale

The VAS is a line that is assessed every 10 cm (100 mm), having two endpoints that correspond to 0 (no pain) and 10 (pain that is as severe as it can be). On a scale, the patients were asked to rate the degree of their pain. The patient’s noted location’s centimeter-distance from the pain-free spot was then used to calculate the intensity of the pain (0 to 10). Mild pain (score up to 3), moderate pain (scoring between 4 and 6), and severe pain (score between 7 and 10).[42,43]

Bromage scale

This four-grade motor block inspection scale is included. Grade 0: unrestricted lower limb movement. Grade 1: Limited to knee bending and unrestricted leg movement. Grade 2: Unable to bend the knee and freely move the leg. Inability to move the lower limbs is Grade 3. The patient’s marked location’s centimeter (0 to 10) distance from the pain-free spot was then used to calculate the severity of pain. Mild pain (score up to 3), moderate pain (scoring between 4 and 6), and severe pain (score between 7 and 10).

Ramsay scale

This scale measures sedation and has six levels. Level 1: Patient is worried and disturbed, restless, or both. Level 2: Patient is cooperative, oriented, calm, and aware of time and place. Level 3: Patient responds exclusively to commands; Level 4: Patient responds quickly to a light glabellar tap or a loud auditory stimulus; Level 5: Patient responds slowly to stimulation with a mild tap on the space between the brows or a loud voice. Level 6: The patient is not responding.

Inclusion and exclusion criteria

Participants in this study were pregnant women aged between 18 and 50 years old, classified as American Society of Anesthesiologists (ASA) I–II according to the ASA physical status classification. Additionally, they were scheduled for optional CS deliveries and had completed vaccination against COVID-19, with the study taking place in the postpandemic period of 2022–2023. The exclusion criteria for this study included several factors related to medical history, physical characteristics, and consent compliance. Participants were excluded if they had a history of drug addiction, moderate to severe cardiac, renal, or neurological diseases, significant spinal deformities such as scoliosis or kyphosis, or coagulation disorders. Additionally, individuals with a height below 130 cm or a body mass index (BMI) greater than 35 were not eligible. Furthermore, the absence of informed consent to participate in the study and the inability to achieve the necessary sensory level following spinal or general anesthesia also led to their exclusion from the study.

Ethical consideration

This study was conducted as a clinical trial following approval from the research ethics committee (IR.MAZUMS.IMAMHOSPITAL.REC.1399.062) and the clinical trial registration (IRCT20161126031095N2) at Imam Khomeini Hospital in Sari. Informed consent was obtained from all patients, and the procedures were thoroughly explained prior to the intervention.

Statistical analysis method

Quantitative measures are described using the mean (standard deviation), while qualitative measures are described using percentages. The research groups were compared statistically using the t-test and qualitatively using the Chi-square test (if necessary, Fisher’s exact test). The variations and severity of pain and movement were quantified using the Bromage, VAS, and Ramsay measures, with variance analysis based on repeated observations. The generalized statistical estimating model (GEE) was used to compare the variance of the aforementioned criteria between the two groups while controlling for the effect of other variables. The statistical significance level of. 05 was used, and all statistical analyses were conducted using STATA-14.

Results

For all 110 patients, neuraxial block was successfully performed in the first attempt. The results of basic demographic and clinical characteristics of the individuals are given in Table 1 concerning the study groups.

Table 1.

Basic demographic and clinical characteristics of patients in Group 1 (receiver of bupivacaine + dexmedetomidine) and Group 2 (receiver of bupivacaine + neostigmine)

Variable	Dex + Bup (n=55)	Neo + Bup (n=55)	P
Age (mean±SD)	32.35±5.7	30.78±6.1	0.17
Education Frequency (percentage)
Upper secondary	35 (63.9)	39 (70.9)	0.42
Academic education	20 (36.4)	16 (29.1)
Diabetes mellitus (%)	11 (20)	10 (18.2)	0.81
Smoking (%)	7 (12.7)	5 (9.1)	0.54
BMI (mean±SD)	33.79±6.08	35.03±3.91	0.21
MAP (mean±SD)	97.98±10.01	100.89±7.76	0.09
SPO2 (mean±SD)	99.42±0.85	99.31±0.81	0.49
Duration of surgery (mean±SD)	65.45±14.25	65.73±12.22	0.91
Duration of anesthesia (mean±SD)	86.91±12.60	88.09±12.08	0.62

SD=Standard deviation, BMI=Body mass index, MAP=Mean arterial blood pressure

The median of the average reduction in arterial blood pressure in groups 1 and 2 was 20 (15–25) and 20 (15–22) mmHg, respectively, and no statistically significant difference was spotted between these two groups (P = .35). Also, the average Apgar score of the babies born in the first and fifth m in both groups was 9 (8–9) and 10 (10–10), respectively, and there was no statistically meaningful difference between the two groups (P = .99). The median of heart rate reduction in groups 1 and 2 was 15 (15–20) and 20 (20–25), respectively, which suggested a statistically significant difference between the two groups (P < .001) [Figure 1].

Figure 1.

Average reduction of mean arterial blood pressure in the studied groups

Figure 1 illustrates the average decrease in blood pressure between the baseline and the lowest recorded value postspinal anesthesia for both study groups. It provides a visual comparison of the hypotensive effects of dexmedetomidine and neostigmine as adjuvants to bupivacaine.

As observed in Figures 2 and 3 and Table 2, pain intensity displayed an upward trend over time, and these changes were statistically significant (P < .001) (the effect of time).

Figure 2.

The trend of pain intensity changes in the studied groups

Figure 3.

Changes in the intensity of sedation in the studied groups

Table 2.

Examination of pain intensity, sedation and movement block at different times in the two study groups. mean (standard deviation)

Variable	Time					Effects
	Start of study	2 h	4 h	8 h	12 h	Time	Between groups	Interaction
VAS
Group 1	0 (0)	1.78 (0.57)	3.13 (0.64)	4.57 (0.88)	4.67 (0.96)	<0.001	<0.001	0.001
Group 2	0 (0)	2.05 (0.65)	1.78 (0.84)	5.71 (0.79)	6.27 (0.87)
Bromage
Group 1	3 (0)	2 (0)	0 (0)	0 (0)	0 (0)	N/A	N/A	N/A
Group 2	3 (0)	2 (0)	0 (0)	0 (0)	0 (0)
Ramsay
Group 1	3 (0)	2 (0)	2 (0)	1.96 (1.24)	1.91 (0.29)	<0.001	<0.001	0.001
Group 2	3 (0)	2 (0)	1.87 (0.34)	1.58 (0.49)	1.42 (0.49)

This figure depicts the temporal changes in pain intensity scores over time for both study groups. It visually represents the evolution of pain perception postoperatively and highlights the differences in pain relief between the dexmedetomidine and neostigmine groups. The level of pain intensity in group 1 was lower than that of group 2, and the difference was statistically meaningful (P < .001) (the intergroup effect). The variations of pain intensity in group 1 differed from that of group 2, and this difference was statistically significant (P < .001) (the interaction effect). In the GEE model, after controlling the effects of the variables: age, BMI, and MAP, the average level of pain intensity score in group 2 was found as 0.75 (confidence limits 95% equal to 0.59–0.91) units more than group 1 (P < .001).

The Bromage score level of all subjects before and 2 h after surgery was 3 and 2, respectively, and no statistically meaningful difference popped up between the two groups [Table 2].

As depicted in Figure 3 and Table 2, the intensity level of sedation varied a lot over time, and these changes were statistically significant (P < 0.001) (the effect of time).

This figure illustrates the changes in sedation scores over time for both study groups. It visually compares the sedative effects of dexmedetomidine and neostigmine, demonstrating their impact on patient alertness and responsiveness postoperatively. The intensity level of sedation in group 2 was lower than that of group 1 and the difference was statistically significant (P < .001) (the intergroup effect). The nausea’s severity variation in Group 2 was different from that of group 1, and this difference was statistically tangible (P < .001) (the interaction effect). In the GEE model, after controlling the effects of the variables as age, BMI, and MAP, the average score of sedation intensity in group 2 was reported as 0.21 (the confidence limits 95% equal to 0.15–0.27) units was less than group 1 (P < .001).

Discussion

This study aimed to evaluate the comparative effects of dexmedetomidine and neostigmine as adjuvants to spinal anesthesia for CS.

The findings of the present study demonstrated that dexmedetomidine significantly reduced postoperative pain intensity compared to neostigmine. While both groups experienced a gradual increase in pain over time, the magnitude of this increase was significantly lower in the dexmedetomidine group. Dexmedetomidine is an alpha-2 adrenergic agonist that provides analgesia through central mechanisms, primarily by inhibiting the release of norepinephrine in the locus coeruleus and enhancing descending inhibitory pathways in the spinal cord.[44,45] In Goodarzi’s study, the results showed that the dexmedetomidine group experienced significantly lower pain scores during recovery and at 2, 6, and 12 h postsurgery compared to the tramadol and neostigmine groups. Additionally, the duration of analgesia was notably longer in the dexmedetomidine group, and the mean analgesic consumption at 24 h postoperation was lower than in the other groups. Overall, while all three adjuvant drugs improved analgesia duration and reduced postoperative pain when combined with lidocaine, dexmedetomidine proved to be the most effective.[46] The results of Al-Metwalli et al. study demonstrated that the analgesic effects of dexmedetomidine are superior for postoperative pain relief compared to traditional analgesics like neostigmine in patients undergoing arthroscopic knee surgery.[47]

Conversely, dexmedetomidine resulted in greater sedation compared to neostigmine. These findings align with previous research, which has shown dexmedetomidine to provide superior analgesia and prolong the duration of sensory and motor block when used as a spinal anesthetic adjuvant. Although neostigmine may offer some analgesic benefits, its potential for side effects, such as nausea and a greater decrease in heart rate, warrants further investigation and careful consideration in clinical practice. These findings highlight the importance of selecting appropriate adjuvants based on their specific pharmacological profiles and the desired clinical outcomes for each patient.

Selecting different combinations and proper doses is a vital process when using adjuvant drugs together with local anesthetics, and it means considering the factors such as the formation and duration of sensory and motor block, the quality and duration of postoperative analgesia and the due side effects that may be spotted in parturient women and newborns.[48,49] Over the years, many medications have been used as adjuvants for spinal anesthesia to prolong preoperative and postoperative analgesia.[50] The findings of the present study showed that intensity of pain increasing over time in both groups, and the changes as statistically significant. The level of pain intensity in group 1 was significantly lower than that of group 2. The pain intensity changes in group 2 were different from those in group 1, which was statistically significant between the two groups. At last, after controlling the effects of the variables as age, BMI, and MAP, the results indicated that the average level of pain intensity score in group 2 was significantly higher than that of group 1.

The findings of the present study showed that sedation intensity critically varied over time and the changes were statistically significant. The sedation intensity level in group 2 was significantly lower than that of group 1. A tangible difference was reported in the severity of nausea changes between the two groups. Finally, after controlling the effects of the variables: age, BMI and MAP, the results showed the average level of sedation intensity score in group 2 being significantly lower than that of group 1. In the present study, no significant difference was observed in the basic demographic and clinical characteristics of the patients in the two groups. In the study by Teymourian et al., the onset of postoperative pain got delayed in the BVD (bupivacaine plus dexmedetomidine) group. The sedation score got improved in the BVD group with the lowest value from 0–3 to 1–4. In terms of Apgar score, no significant difference was seen between the two groups. Besides, in terms of bispectral index (BIS) during CS, there was a significant difference between the two.[51] Although in our research, the difference between the two groups was not investigated in terms of BIS, but the results of the mentioned research and the present study denoted that using intrathecal DEX as an auxiliary medication in CS surgery can lower intraoperative and postoperative analgesia exerting no effect. In the study by Bi et al., 60 pregnant women were given spinal anesthesia using intrathecal Bupi (10 mg) or in combination with dexmedetomidine (3 and 5 μg) for CS. The concurrent administration of dexmedetomidine (3 and 5 μg) increased the duration of motor and sensory block compared to bupivacaine (10 mg) alone. In the dexmedetomidine groups (3 and 5 μg), lower dose of lidocaine and fentanyl was required. Six hours after surgery, the VAS was smaller in the dexmedetomidine administration groups (3 and 5 μg), which was consistent with the findings of the current study. Nevertheless, in this research, uterine contraction pain 6 and 12 h after surgery and supplemental pain reliever showed no difference in the three groups.[52]

By prolonging the sensory block accompanied with reduced release of neurotransmitters from the C-fibers of the spinal cord.[52] Spinal dexmedetomidine was administrated in doses ranging from about 3 to 15 μg.[16,17,42,53,54,55] However, the optimal dose of spinal dexmedetomidine was not precisely fixed. Sullivan et al. found out that the required dexmedetomidine for ED50 to inhibit C-fiber responses of horn neurons was 2.5 μg, and β-evoked responses were inhibited to a lower rate with the greatest inhibition at doses above 10 μg.[43] Therefore, in this study, a dose of less than 2.5 μg was used to provide adequate postoperative analgesia.

Spinal neostigmine has advantages over some currently used spinal medications because it does not cause hypotension, sedation, respiratory depression, or neurological dysfunction.[56,57] In the research by Singh et al., the quality of motor and sensory block in both groups, i.e. the ropivacaine + DEX and the ropivacaine + NEOS, was critically better than that of the ropivacaine group. However, dexmedetomidine was a better adjuvant compared to neostigmine because of its rapid onset of anesthesia, better intraoperative and postoperative analgesia, and the prolongation of motor and sensory block without a significant increase in the side effects, which confirmed the present study derived results. The research by Singh et al. indicated that the side effects such as nausea and vomiting were the highest in the ropivacaine + NEOS group and statistically significant compared to other groups.[56] In the present study, a meaningful difference was found in the severity variation of nausea between the two groups. Also, there was no significant difference in terms of the decrease in MAP and the Apgar score of the newborns between the two groups. However, the median of decreased heart rate in groups 1 and 2 was 15 and 20, respectively, and the observed difference between the two groups was statistically significant (P < .001), which signifies the greater effect of neostigmine on heart rate decrease. Covid-19 has been an interventionist in all areas of life, including the living environment and individual behaviors. Because of interferences of COVID-19 in patient this study after overall vaccination at the end of COVID-19 pandemic in 2022 to 2023 this research is done[58,59,60,61,62,63,64,65].

Conclusion

This study aimed to assess the efficacy of dexmedetomidine and neostigmine as adjuvants to spinal anesthesia in reducing post-CS pain and sedation. Our findings indicate that the addition of dexmedetomidine to spinal anesthesia significantly reduced postoperative pain intensity compared to neostigmine. Additionally, dexmedetomidine resulted in lower sedation scores and a less pronounced increase in nausea compared to neostigmine. These results align with previous research, which has demonstrated the analgesic and sedative properties of dexmedetomidine. Its mechanism of action, involving α₂-adrenergic receptor agonism, contributes to its effectiveness in prolonging sensory and motor block, reducing neurotransmitter release, and providing postsynaptic hyperpolarization of neurons. While neostigmine, a cholinesterase inhibitor, can enhance local anesthetic block by increasing acetylcholine levels, it may be associated with a higher incidence of side effects such as nausea and vomiting. Finally, dexmedetomidine appears to be a more effective and safer adjuvant for spinal anesthesia in CS, providing superior pain relief and reduced sedation compared to neostigmine. Further research may be needed to optimize the dosage and timing of dexmedetomidine administration to maximize its benefits.

Limitations and recommendations

The study has several limitations that may impact the validity and applicability of its findings. First, the sample size was relatively small, comprising only 110 participants; a larger randomized controlled trial would enhance the generalizability of the results and provide stronger statistical power to detect differences between treatment groups. Additionally, conducting the research at a single institution may restrict the applicability of the findings to other settings, as variations in practices, patient demographics, and institutional protocols could influence outcomes. The follow-up duration for assessing pain intensity and sedation was also limited to just 12 h postsurgery. Extending this period would offer valuable insights into the long-term effects of dexmedetomidine and neostigmine on postoperative pain management.

Consent for publication

Written informed consent was obtained from the participants and the procedure, objectives, and consequences of the study were explained and it was announced that they could withdraw from participating in the study at any time.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

This article is an extract from the residency thesis and was done under the support of Mazandaran University of Medical Sciences Research and Technology Vice-Chancellor.